Abstract: DNA cloning shuttle vectors, including a cosmid shuttle vector, for E. coli and Streptomyces are disclosed. Specifically, disclosed shuttle vectors pAL7002 (NRRL B-18055) and pNJ1 (NRRL B-18054) contain an E. coli origin of replication, Streptomyces replication functions, and antibiotic resistance markers for both E. coli and Streptomyces. In addition, pNJ1 contains a cos sequence. Novel 2-norerythromycin antibiotics A, B, C, and D, which were produced in a strain Streptomyces erythreus 12693-240 (NRRL B-18053) transformed by pNJ1 bearing DNA from Streptomyces antibioticus, are also disclosed. The present invention also provides a method for producing novel antibiotics. This method for antibiotic production is applied to the transformation of a blocked mutant of S. erythreus with genomic DNA from S. antibioticus but may be more broadly applied to genes of antibiotic-producing strains transformed into cells which are blocked in the pathway for production of a different antibiotic.

Abstract: Novel 6-deoxyerythromycin derivatives are disclosed, as are methods for their preparation and use as antiinfective agents. The compounds of the invention include 6-deoxyerythromycins and 6-deoxy-15-norerythromycins which are represented by the structural formula ##STR1## in which R.sub.1 is selected from OH and H, and R.sub.2 and R.sub.3 are independently selected from H and CH.sub.3, as well as the pharmaceutically acceptable salts and esters of the above compounds. Additionally disclosed are genetically modified microorganisms which produce the compounds of the invention and means for the preparation of those microorganisms.

Abstract: The present invention relates to a basic protein called phospholipase A2 (PLA2), isolated from the venom of a snake of the family Elapidae, especially of a Naja snake and more particularly Naja nigricollis and/or Naja mossambica pallida, to the fragments and derivatives of the said protein, to their methods of preparation, to pharmaceutical compositions which can be used in human and/or veterinary medicine, and to diagnostic agents in which the said protein and/or its derivatives and/or its fragments are present.The said protein comprises 118 amino acids, its molecular weight is of the order of 13,300 Daltons and its isoelectric point is of the order of 8.6.The derivatives of the said protein are modified at one of the histidines by fixation of an alkyl group of the formula R--CH.sub.2 --X.Application to the detection of tumoral cells are discussed.

Abstract: A method for producing streptovaricin by culturing a streptovaricin producing strain in the presence of a nonionic adsorbent. This procedure substantially increases the production efficiency of the streptovaricin. A second embodiment wherein the streptovaricin producing strain is produced in the presence of fumaric acid or its water soluble salts to provide improvements in production efficiency is also disclosed.

Abstract: Fermentation of S. erythraea produces the novel avermectin, 28-hydroxy ivermectin aglycone.

Abstract: A method is disclosed for the quantitative determination of 1,4-dihydronicotinamide adenisne dinucleotide (NADH) in solution. The method comprises contacting the NADH-containing solution with an activated carbon electrode, maintaining the carbon electrode at a controlled, fixed potential effective to cause oxidation of NADH at the electrode surface, and measuring the current output from the carbon electrode, wherein there is used a noble metal containing preferably a platinized or palladized activated carbon electrode comprising a porous, heterogeneous, resin-bonded layer of activated carbon or graphite particles comprising the finely divided noble metal preadsorbed thereon and bonded together with a natural or synthetic resin binder, preferably a hydrophobic resin such as polytetrafluoroethylene.

Abstract: There are disclosed new compounds with significant antiparasitic activity which are prepared by fermenting 13-epi-ivermectin aglycone in a novel microorganism identified as Streptomyces avermitilis MA-5542. The 13-epi-ivermectin aglycone compounds are modified by the microorganism by methylation at the 5-hydroxy position and the addition of an .alpha.-L-oleandrose at the 13-position hydroxy. The compounds are significant antiparasitic and anthelmintic agents and compositions for that use are also disclosed.

Abstract: Compounds of formula (1) ##STR1## wherein R represents a sugar residue or an acylated derivative thereof;R.sup.1 represents a methyl, ethyl or isopropyl group;Y.sup.1 is --CH.sub.2, Y.sup.2 is --CH-- and X represents ##STR2## [wherein R.sup.2 represents a hydrogen atom or a group OR.sup.6 (where OR.sup.6 is a hydroxyl group or a substituted hydroxyl group having up to 25 carbon atoms) and R.sup.3 represents a hydrogen atom, or R.sup.2 and R.sup.3 together with the carbon atom to which they are attached represent >C.dbd.0, >C.dbd.CH.sub.2 or >C.dbd.NOR.sup.7 (where R.sup.7 represents a hydrogen atom, a C.sub.1-8 alkyl group or a C.sub.3-8 alkenyl group) and the group >C.dbd.NOR.sup.7 is in the E configuration] or --Y.sup.1 --X--Y.sup.2 -- represents --CH.dbd.CH--CH-- or --CH.sub.2 --CH.dbd.C--; andR.sup.4 represents a group OR.sup.6 as defined above and R.sup.5 represents a hydrogen atom, or R.sup.4 and R.sup.5 together with the carbon atom to which the are attached represent >C.dbd.0 or >C.

Abstract: Antiparasitic compounds of formula (I): ##STR1## The broken line at the 22-23 position representing an optional double bond and either R.sup.1 is H or OH and the double bond is absent or the double bond is present and R.sup.1 is absent; R.sup.2 is optionally substituted phenyl, or a group of formula (II): ##STR2## wherein X is O, S or --CH.sub.2 --, abc and d are 0-2 and a+b+c+d.ltoreq.5 R.sup.3 is H or MeR.sup.4 is H, OH or 4'-(alpha-L-oleandrosyl)-alpha-L-oleandrosyloxy.The compounds are prepared by fermentation of Streptomyces avermitilis in the presence of an N-alkanoyl cysteamine thioester containing R.sup.2.

Abstract: A new acidic polycyclic ether antibiotic UK-58,852 has the formula: ##STR1## wherein R and R.sup.1 are both hydrogen, and can be prepared by the submerged aerobic propagation in aqueous nutrient media of Actinomadura sp. ATCC 39697. The antibiotic and its cationic salts are active against a variety of microorganisms and are effective in controlling coccidiosis, enteritis, swine dysentery and theileriosis as well as being effective in promotion of growth and/or improving efficiency of feed utilization in swine and ruminants. Two minor components, wherein R is H and R.sup.1 is CH.sub.3 and wherein R and R.sup.1 are both CH.sub.3, have also been isolated from the fermentation.

Abstract: Spiramycin antibiotic biosynthetic genes of Streptomyces ambofaciens are provided by the present invention, in addition to a variety of recombinant DNA vectors. The genes also function in other macrolide producing organisms. The genes can be used to increase or otherwise alter the macrolide antibiotic-producing ability of an organism. The present invention also provides host strains comprising mutant spiramycin biosynthetic genes which can be used to generate novel antibiotics. Also provided is a method for preparing the mutant gene comprising mutating cloned spiramycin biosynthetic DNA by transposon mutagenesis with subsequent transformation into a macrolide-antibiotic producing host and homologous recombination into its genome, to generate stable mutant cell lines.

Abstract: Disclosed is a means useful for selectively inhibiting human tissue plasminogen activator utilizing a thrombin inhibitor, illustrated by D-Phe-Pro-Arg-chloromethyl ketone (PPACK), thus providing a novel assay system for measuring human tissue plasminogen activator activity.

Abstract: Cyclic peptides are produced by the controlled aerobic fermentation of Streptomyces silvensis, ATTCC No. 53525 or ATCC No. 53526. These compounds are antagonists of oxytocin and are useful in the treatment of preterm labor and vasopressin and are thus useful in the treatment and prevention of disease states wherein vasopressin may be involved, for example congestive heart failure, hypertension, edema and hyponatremia.

Abstract: Conjugates of salicylic acid and certain poly(amino acids), which are either antigenic or enzymes, are provided. Antibodies raised against the antigenic poly(amino acids) and the enzyme conjugates are used as reagents in immunoassays.

Abstract: A antibiotic L53-18A and a pharmaceutically acceptable salt thereof which are useful for treatment of bacterial inventions are obtained by culturing, for example, Saccharopolyspora sp. L53-18 (FERM BP 2231) in a medium and the antibiotic accumulated therein is collected.

Abstract: Pancreatic .alpha.-amylase is determined in body fluid in the presence of salivary .alpha.-amylase by combining the body fluid with a monoclonal antibody that inhibits salivary .alpha.-amylase by 95% or more and inhibits pancreatic .alpha.-amylase by 50% or less, and then detecting pancreatic .alpha.-amylase with a system for the detection of .alpha.-amylase. The monoclonal antibody may be in immobilized form. The monoclonal antibody is preferably produced by immunizing a Balb/c mouse or an AJ mouse with a specific immunogen for a specific number of times, fusing .beta.-lymphocytes obtained from the mouse with a myeloma cell line to form an antibody producing hybridoma cell line, cloning and screening the hybridoma cell line for the desired monoclonal antibody, and isolating the monoclonal antibody. The immunogen contains modified or unmodified salivary .alpha.-amylase, aluminum hydroxide and Bortadella pertussis.

Abstract: Incubation of 13-deoxy ivermectin aglycone with a species of B. subtilis and of S. griseus results in the production of 13-.beta. ivermectin monoglucopyranoside as the major product and of 5-.beta. ivermectin monoglucopyranoside as the minor product.

Abstract: The present invention discloses a method for producing a novel antibiotic, 2"'-O-demethyltylosin. The novel antibiotic, utilizing recombinant DNA technology, can be produced from a transformed mutant of a tylosin producing microorganism. By transforming for example Streptomyces fradiae GS 16 with plasmid pHJL284, the transformant can produce 2"'-O-demethyltylosin. Streytomyces fradiae GS16 is a tylosin producing species that contain a mutation in the tylE gene found in the tylosin biosynthetic pathway. The tylE gene codes for demethylmacrocin 2"'-O-methyltransferase enzyme (DMOMT), the enzyme that methylates the 2-hydroxyl position of the 6-deoxyallose moiety. Plasmid pHJL284 contains the cloned tylF gene which codes for the macrocin 3"'-O-methyltransferase enzxyme (MOMT), the enzyme that methylates the 3"'-hydroxyl position, but it does not contain the tylE gene. Transformation of S.

Abstract: Compounds of formula (II): ##STR1## wherein R.sup.3 is optionally protected hydroxy; one of R.sup.4 and R.sup.5 is optionally protected hydroxy; and the other of R.sup.4 and R.sup.5 is hydrogen, which are obtainable by the fermentation of a Streptomyces microorganism, have anthelmintic activity.

Abstract: A method for evaluating cyclosporine-related nephrotoxicity in a patient receiving cyclosporine therapy is disclosed. The method comprises measuring urine kallikrein content utilizing radioimmunoassay specific for human urine kallikrein. The value obtained is compared then to a pre-treatment value of urine kallikrein levels.Also disclosed is a means for predicting susceptibility to cyclosporine-related nephrotoxicity. Potential cyclosporine therapy patients are evaluated according to their baseline (pre-treatment) urinary kallikrein levels. Low initial levels of urine kallikrein are predictive of susceptibility to cyclosporine-related nephrotoxicity.Also disclosed is a method for monitoring cyclosporine-related nephrotoxicity during the course of cyclosporine treatment. Decreased urinary kallikrein indicates that cyclosporine administration should be decreased or terminated. Increased urinary kallikrein indicates that cyclosporine administration may be increased or maintained.

Abstract: The present invention relates to a method for identifying or shielding functional sites or epitopes of proteins that enter the exocytotic pathway of eukaryotic cells (transportable proteins) by the addition of supernumerary N-linked oligosaccharide side chains at chosen sites on the surface thereof using oligonucleotide mutagenesis. The present invention also relates to mutant transportable proteins having supernumerary N-linked oligosaccharide side chains which shield functional sites or epitopes; and genes which encode the same.

Abstract: A .beta.-galactosidase complementation assay for determining the presence of an analyte which is a member of a specific binding pair (sbp) in a sample is provided, which assay permits visual discrimination between those samples wherein the analyte is present above a predetermined, threshold concentration. The method comprises combining the sample with a hydrophobic enzyme donor- (ED-) analyte conjugate and the complementary member of the sbp to form an sbp complex-containing assay medium. A small volume of the assay medium is spotted onto an enzyme acceptor (EA) affixed to a bibulous, solid support, followed by development with enzyme substrate solution. A substantially larger area is detectable when analyte in the sample is below as compared to above a threshold concentration. The assay is particularly useful in field testing applications such as determining the presence of antibiotics in milk, toxins in water, or drugs in serum or urine. Kits facilitating the method are also provided.

Abstract: A method is provided for combining normally interacting reagents in a liquid single reagent and preventing complex formation using a surfactant and then reversing the inhibition by adding a cyclodextrin. The method finds particular use in diagnostic immunoassays. Reagents facilitating the invention are also provided.

Abstract: This invention relates to an antibiotic NK86-0279 of the formula: ##STR1## which exhibits antifungal, antitumor, vascularizations-inhibitory and insecticidal activities.

Abstract: Mucor circinelloides f. griseo-cyanus IFO 4563 is cultivated in a medium containing 6-O-methylerythromycin A as a substrate to obtain 14-hydroxy-6-O-methyl-erythromycin A. This compound and its salt have anti-bacterial activity.

Abstract: An antibiotic complex, containing three major components, has been isolated from fermentations of a new strain of the microorganism Streptomyces hirautus. The major components are new, neutral, macrolide antibiotic compounds, which are useful as antibacterial agents against certain gram-positive bacteria.

Abstract: The carG gene of Streptomyces thermotolerans has been isolated and used to construct recombinant DNA expression vectors. The carG gene encodes the activities required for the biosynthesis of the 16-member cyclic lactone of carbomycin. The carG gene can be used not only to construct recombinant cells with an increased ability to produce carbomycin but also to construct recombinant cells with the ability to produce novel antibiotic compounds.

Abstract: The carB gene is a novel carbomycin resistance-conferring gene isolated from Streptomyces thermotolerans and used to construct a number of cloning vectors for use in Streptomyces and related organisms. One such coloning vector, plasmid pOJ159, can be obtained in S. griseofuscus C581 under the accession number NRRL 18090. S. lividans and S. griseofuscus are the preferred hosts when the carB gene is used to select carbomycin-resistant Streptomyces transformants.

Abstract: Compounds as described having the partial formula ##STR1## These compounds may have a 5-OH or --OMe group amd at the 25- position an isopropylene group substituted by methyl, ethyl or isopropyl.The compounds may be used in agriculture or medicine as antiparasitics, and may be prepared by culturing certain Streptomyces strains, in particular Streptomyces thermoarchaensis NCIB 12015.

Abstract: There are disclosed macrolides isolated from the fermentation broth, with avermectin Bla, avermectin Blb or 22,23-dihydro avermectin Bla as a substrate, of a known microorganism identified as MA-6181. The structure of the novel compounds isolated from the microorganism are presented based upon analytical studies. The compounds are highly potent antiparasitic, insecticidal, and anthelmintic agents. Compositions for such uses are also disclosed.

Abstract: A new method is provided for forming crystals of amphotericin B directly in fermentation broth which crystals are easily separable without use of costly solvent extraction techniques which method includes a direct microbial cell autolysis step to induce crystal formation.

Abstract: An anthracycline compound, Arugomycin, having the physicochemical properties set forth below is produced by aerobically cultivating an Arugomycin-producing Streptomyces strain in a suitable culture medium, and recovering from the culture the anthracycline compound, Arugomycin.(1) Color and form:Orange powder(2) Melting point:207.degree. to 213.degree. C. (decomposed)(3) Specific rotatory power:[.alpha.].sub.D.sup.25 =+112.degree.(C: 0.1, chloroform:methanol=9:1)(4) Elementary analysis (%):______________________________________ C H O N ______________________________________ Found 56.2 6.9 35.1 1.8 Calcd. 56.7 6.7 34.9 1.7 ______________________________________(5) Ultraviolet and visible absorption spectrum: as shown in FIG. 1. ______________________________________ .lambda..sub.max (E.sup.1% .sub.1cm) ______________________________________ CH.sub.3 OH 235(363), 258(167), 292(61), 476(104) 0.1N HCl + CH.sub.3 OH 235(387), 258(159), 292(61), 468(110) 0.1N NaOH + CH.sub.

Abstract: The present invention relates to a novel polyether ionophore antibiotic of the formula ##STR1## and its pharmaceutically acceptable salts. The compound of formula I and its salts exhibit activity as an antibacterial agent and as an anticoccidial agent.

Abstract: Fermentation of a culture of Nocardia sp. ATCC 39043 produces an antibiotic complex comprising erythromycin D, 3",4"-di-O-acetylerythromycin D, 3"-O-acetyl-4"-O-propionylerythromycin D and 4"-O-acetylerythromycin D. The components are separated and are each useful in vitro and in vivo as antibacterial agents. If erythromycin D is the desired product, the esters can be hydrolyzed prior to the separation of the erythromycin D.

Abstract: The fermentation of a substrate selected among erythronolide B, erythronolide A and erythronolide A oxime with a novel mutant, Streptomyces antibioticus ATCC 31771, obtained from an industrial stock for the production of oleandomycin, said novel mutant being incapable of producing the same oleandomycin, permits novel macrolide antibiotics to be produced, having not only an activity range like that of erythromycin, but characterized by a greater stability in acidic environment, whereby for the administration of the antibiotic it is no longer necessary to have recourse to esters and/or salts highly toxic for the organism.

Abstract: New macrocin and lactenocin ester derivatives of the formula: ##STR1## wherein R is formyl or hydroxymethyl; R.sup.1 is hydrogen, acetyl or propionyl; R.sup.2 is hydrogen or ##STR2## and R.sup.3 is hydrogen, acetyl, propionyl, n-butyryl or isovaleryl; provided that one of R.sup.1 or R.sup.3 must be other than hydrogen; and the acid addition salts thereof; prepared by bioconversion of macrocin or lactenocin with an acylating enzyme system produced by Streptomyces thermotolerans strains, have improved activity against Mycoplasma species.

Abstract: A new acidic polycyclic ether antibiotic, CP-63,517, having the formula: ##STR1## and cationic salts thereof produced by submerged aerobic propagation of Streptomyces endus subsp. aureus, ATCC-39574, a new strain of microorganism isolated from a soil sample in Japan, a process for producing this antibiotic and methods for its use to improve feed utilization, promote growth of cattle and swine and to control coccidiosis.

Abstract: An antibiotic complex, consisting of one major and two minor components, has been isolated from fermentation of a new Streptomyces culture. The components from the complex are three new macrolides which are active as antibacterial agents against certain gram-negative and gram-positive microorganisms.

Abstract: 20-Dihydro-20-deoxy-23-de(mycinosyloxy)tylosin (20-deoxo-DMOT), specified 2'-acyl ester derivatives, and their acid addition salts are useful intermediates and antibacterial agents. Methods of preparing 20-deoxo-DMOT and 5-O-mycaminosyltylactone by fermentation of Streptomyces fradiae ATCC 31733 are included.

Abstract: Fermentation of a culture of Nocardia sp. ATCC 39043 produces an antibiotic complex comprising erythromycin D, 3",4"-di-O-acetylerythromcyin D, 3"-O-acetyl-4"-O-propionylerythromycin D and 4"-O-acetylerythromycin D. The components are separated and are each useful in vitro and in vivo as antibacterial agents. If erythromycin D is the desired product, the esters can be hydrolyzed prior to the separation of the erythromycin D.

Abstract: The antibiotics S 54832/A-I, S 54832/A-II, S 54832/A-III and S 54832/A-IV are obtained from a new Micromonospora globosa strain.

Abstract: Antibacterial 9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin D, pharmaceutically-acceptable salts thereof, pharmaceutical compositions comprising antibacterially-effective amounts thereof, a method of treatment of bacterial infections with antibacterially effective amounts thereof, and intermediates for the synthesis thereof from erythromycin D.

Abstract: An antibiotic complex, consisting of two major components, has been isolated from fermentations of a new subspecies of Streptomyces albus culture. The two major components from the complex are two new macrolide antibiotics, which are active as antibacterial agents against certain gram-positive and gram-negative microorganisms.

Abstract: 20-Dihydro-20-deoxy-23-de(mycinosyloxy)tylosin (20-deoxo-DMOT), specified 2'-acyl ester derivatives, and their acid addition salts are useful intermediates and antibacterial agents. Methods of preparing 20-deoxo-DMOT and 5-O-mycaminosyltylactone by fermentation of Streptomyces fradiae ATCC 31733 are included.

Abstract: 23-Demycinosyltylosin (DMT) which has the formula: ##STR1## 20-dihydro-DMT, specified acyl ester derivatives, and their acid addition salts are useful antibacterial agents. Improved methods of making 5-O-mycaminosyltylonolide (OMT) and 20-dihydro-OMT by mild acid hydrolysis of DMT and 20-dihydro-DMT, respectively, are included.

Abstract: 20-Dihydro-20-deoxy-23-demycinosyltylosin (DH-DO-DMT), 20-dihydro-20-deoxy-5-O-mycaminosyltylonolide (DH-DO-OMT), specified acyl ester derivatives, and their acid addition salts are useful intermediates and antibacterial agents. Methods of preparing DH-DO-DMT and DH-DO-OMT by fermentation of Streptomyces fradiae and the microorganism S. fradiae ATCC 31733 are included.

Abstract: There is disclosed a macrolide isolated from the fermentation broth of a microorganism identified as MA-5285 which morphological analysis reveals to be a strain of Streptomyces hygroscopicus. The compound's structure is presented based upon analytical studies. The compound has insecticidal and antiparasitic activity.

Abstract: There is disclosed novel derivatives of C-076 compounds wherein the 22-position, normally substituted, is substituted with a hydroxy group. The compounds are isolated from the C-076 fermentation broth of Streptomyces avermitilis. The compounds have potent anthelmintic, insecticidal, and acaricidal activity and compositions for that use are also disclosed.

Abstract: 2'"-O-demethylmacrocin (DOMM) which has the formula: ##STR1## 20-dihydro-DOMM, 2'"-O-demethyllactenocin (DOML), 20-dihydro-DOML, specified acyl ester derivatives, and their acid addition salts are useful antibacterial agents.

Abstract: There are disclosed certain new compounds related to C-076 compounds which have been produced by a mutant of the culture that produced the original C-076 compounds and isolated from the fermentation broth thereof. The compounds retain the C-076 16-membered cyclic backbone, however, the groups attached thereto are considerably modified from the original C-076 compounds. The new compounds have been found to retain the biological activity of the parent C-076 compounds. The compounds are thus potent antiparasitic agents and compositions and methods for such uses are also disclosed.